New cardiac warning for fluoroquinolones

Recalls, warnings, and alerts

A warning about an increased risk of ruptures or tears in the aorta when certain patients
use fluoroquinolones. An FDA review found that the antibiotics, given by mouth or through an injection,
can increase the occurrence of aortic aneurysm or dissection. The estimated background
risk ranges from nine aortic aneurysm events per 100,000 people per year in the general
population to 300 aortic aneurysm events per 100,000 people per year in individuals
at the highest risk. Fluoroquinolones should not be used in patients at increased risk (e.g., those with a history of blockages or aneurysms of the aorta or other blood
vessels, those with hypertension, and the elderly) unless there are no other treatment
options available. A new warning about this risk will be added to the prescribing
information and patient medication guide for all fluoroquinolones.

Image by Getty Images

A class I recall of the CareScape R860 Inspiratory Safety Guard by GE Healthcare due to the risk of disconnection from the ventilated patient's breathing circuit. A manufacturing defect is the cause of the issue. The recall includes 307 devices
manufactured and distributed from August 2017 through September 2018.

A warning that rare but serious cases of stroke and tears in the lining of arteries
in the head and neck have occurred in patients with multiple sclerosis shortly after
they received alemtuzumab (Lemtrada). The FDA has received 13 reports of stroke or cervicocephalic arterial dissection that
occurred shortly after a patient received the drug. In response, the FDA has added
a new warning about these risks to the drug label and patient medication guide and
has also added the risk of stroke to the existing boxed warning. The drug is also
approved under the brand name Campath to treat B-cell chronic lymphocytic leukemia,
and that drug's label will also be updated to include these risks. Clinicians should
advise patients at every infusion of the drug to seek immediate emergency medical
attention if they experience symptoms of ischemic or hemorrhagic stroke or cervicocephalic
arterial dissection. Because early symptoms such as headache and neck pain are not
specific, clinicians should promptly evaluate patients who report symptoms consistent
with these conditions.

An alert not to use drug products intended to be sterile that were produced and distributed
by Promise Pharmacy due to lack of sterility assurance. During an FDA inspection of the company's facility, investigators observed insanitary
conditions, including poor sterile production practices and inadequate design of one
of its processing rooms. The FDA has recommended that the company recall all unexpired
drug products intended to be sterile and cease sterile operations until adequate corrections
are made. While the company agreed to cease sterile operations in the inadequately
designed processing room, it did not recall drug products it compounded in that room.

A warning that signs and symptoms of differentiation syndrome are not being recognized
in patients with acute myeloid leukemia who are receiving enasidenib (Idhifa). While the drug's prescribing information and patient medication guide already contain
a warning about the syndrome, the FDA is aware of cases that were not recognized and
patients who did not receive the necessary treatment. Clinicians should describe the
symptoms of differentiation syndrome to patients when starting the drug and at follow-up
visits. The syndrome has occurred as early as 10 days and up to five months after
starting the medicine. Consider a diagnosis of differentiation syndrome if patients experience unexplained
respiratory distress or other symptoms, and treat promptly with oral or IV corticosteroids.

A recall of two lots of losartan potassium tablets USP (100 mg) by Torrent Pharmaceuticals Limited due to detected trace amounts of NDEA in the active pharmaceutical ingredient, manufactured by Hetero Labs Limited. Batches
were distributed nationwide and have an expiration date of April 2019.

A recall of CoaguChek XS Test Strips distributed directly to U.S. consumers by Terrific
Care, LLC./Medex Supply Dist, Inc. The recalled products, which include all catalog/REF numbers that do not end in 160,
were found to inaccurately report high international normalized ratio (INR) test results and were distributed from Dec. 27, 2017, through Dec. 15, 2018. While the manufacturer
previously recalled the test strips, these batches were not included in the recall
because they were not distributed by the manufacturer.

A recall of 20 lots of Dyural-40 and 61 lots of Dyural-80 by Asclemed USA Inc. due to a latex hazard. The convenience kits contain sodium chloride USP (0.9%) that was recalled by manufacturer
Fresenius Kabi due to product labeling incorrectly stating the stoppers do not contain latex.

A class I recall of the BrightMatter Guide with SurfaceTrace Registration by Synaptive Medical due to a software defect. The recall includes 36 of the brain-imaging devices, which were manufactured between
Nov. 17, 2017, and April 24, 2018.

Miscellaneous

A field corrective action for the Puritan Bennett 980 ventilator series by Medtronic
to address customer feedback. A software update will provide product enhancements, including external USB drive
performance and graphical user interface functionality. The ventilators may continue
to be used before the software update is installed.

A safety communication about higher-than-expected rates of duodenoscope contamination
after reprocessing, according to preliminary data from postmarketing surveillance
studies conducted by all three U.S. duodenoscope manufacturers. After reprocessing, up to 3% of properly collected samples tested positive for more
than 100 colony-forming units of organisms that are unlikely to cause serious infections,
an indication of a reprocessing failure. Another 3% of samples tested positive for
organisms of high concern, such as Escherichia coli and Staphylococcus aureus. The manufacturers (Olympus, Fujifilm, and Pentax) are conducting root-cause analyses
to better understand these preliminary culturing results.

A warning letter issued to the manufacturer of the active pharmaceutical ingredient
found in valsartan. The manufacturer, China-based Zhejiang Huahai Pharmaceutical Co., Ltd., is the subject
of an ongoing FDA investigation into the probable cancer-causing impurities N-nitrosodimethylamine and NDEA, which have been found in angiotensin-receptor blockers.
The warning letter outlines several manufacturing violations, including impurity control,
change control, and cross-contamination from one manufacturing process line to another.
The FDA is still investigating the root cause of the impurity.

Approvals

A mobile medical application to help increase retention in an outpatient treatment
program for individuals with opioid use disorder. The reSET-O app, a prescription cognitive behavioral therapy, is intended to be used
in addition to outpatient treatment under the care of a health care professional in
conjunction with treatment that includes buprenorphine and contingency management.
It may be downloaded directly to a patient's mobile device after he or she receives
a prescription to do so from a doctor. In a 12-week clinical trial of 170 patients
treated with buprenorphine and a behavior therapy program, with or without a desktop
version of the app, those who used the app had a significant increase in retention
in their treatment program compared to those who did not. However, the app was not
shown to decrease illicit drug use or improve abstinence. It is not intended to be
used as a standalone therapy, as a substitute for medication, or for patients whose
primary language is not English. The app was not associated with side effects.

Gilteritinib (Xospata) tablets to treat adults who have relapsed or refractory acute
myeloid leukemia with a FLT3 mutation, as detected by an FDA-approved companion diagnostic. In a trial of 138 patients, 21% of patients who received the orphan drug achieved
complete remission or complete remission with partial hematologic recovery. Of 106
patients who required red blood cell or platelet transfusions at the start of treatment,
31% became transfusion-free for at least 56 days. Common side effects were myalgia,
arthralgia, fatigue, and elevated liver aminotransferase levels. Clinicians should
monitor patients who are taking the drug for posterior reversible encephalopathy syndrome,
prolonged QT interval, and pancreatitis. Rare cases of differentiation syndrome have
also been reported.

Ravulizumab (Ultomiris) injection to treat adults with paroxysmal nocturnal hemoglobinuria. The drug, a long-acting complement inhibitor that prevents hemolysis, was studied
in a trial of 246 treatment-naive patients who were randomized to receive either the
drug or eculizumab, the current standard of care for the disease. Patients in both
groups had a similar incidence of hemolysis. A second trial of patients who were clinically
stable after six or more months of treatment with eculizumab randomized 195 patients
to receive either continued eculizumab or ravulizumab and found the latter noninferior.
Common side effects were headache and upper respiratory infection. A boxed warning
alerts clinicians about the risk of life-threatening meningococcal infections and
sepsis.

ACP Hospitalist provides news and information for hospitalists, covering the major issues in the field. All published material, which is covered by copyright, represents the views of the contributor and does not reflect the opinion of the American College of Physicians or any other institution unless clearly stated.